Sudden cardiac death (SCD) accounts for approximately 300,000-400,000 deaths per year in the United States. Although the individual risk of SCD in the adult U.S. population is only about 0.1-0.2% per year, when applied to the large population base, SCD is often the first and only manifestation of the presence of a cardiovascular disease in a majority of cardiovascular related deaths. Deaths associated with recovering from large myocardial infarctions actually represent the minority of the total cardiovascular related deaths per year. As a result, a low cost screening tool that would provide early detection of patients at risk for SCD would be tremendously valuable for early treatment and intervention.
However, it can be difficult to accurately predict or assess the risk of SCD because many underlying pathologies support or trigger the events leading to SCD instead of any single condition. Of these various conditions, most data suggests that regulation of the heart through the sympathetic and parasympathetic (vagal) branches of the autonomic nervous systems is extremely important in maintaining stable rhythms. In particular, it appears that vagal stimulation mitigates the development of ventricular arrhythmias in a variety of experimental studies.
One promissory marker related to SCD is the variability of the heart rate under various conditions. For example, studies using Holter records have shown that low heart rate variability (HRV) is a marker for SCD. Holter studies predominately follow individuals over the course of an average day, mostly reflecting low exercise conditions.
In 1993, a study by van Ravenswaaji et al. reviewed four years of published HRV papers and summarized the various time and frequency domain methods for computation of HRV, which remain largely the same today. This study concluded that HRV is an important surveillance tool for post infarction and diabetic patients to prevent SCD. Although HRV was noted as having a higher association with risk for death than other variables obtained by Holter monitoring, this study also concluded that HRV has a rather low positive predictive value in mass screening (less than 20%). Nonetheless, other studies establish that reduced HRV obtained from 24 hour Holter recordings is an independent predictor of death in chronic heart failure patients.
Another study by Arai et al. analyzed HRV in a cohort of patients undergoing exercise testing and found that the power in the low frequency band [0.03-0.15 Hz] systematically decreased with an increase in exercise and rebounded during recovery after exercise. The low frequency band may be modulated by both the sympathetic and parasympathetic nervous system related to baroreflex activity, temperature regulation and maintenance of homeostasis. The low frequency response to exercise testing was found to be muted in patients with severe congestive heart failure. Conversely, this study found that power in the high frequency band [0.15-0.8 Hz] increased with exercise, decreased through recovery and was highly correlated to respiration—the respiration sinus arrhythmia effect.
Many of the HRV studies have been predicated upon an assumption that a balance between the operation of the parasympathetic (vagal) and sympathetic arms of the autonomic nervous system controls heart rate. For example, as the heart rate increases it has been assumed that sympathetic control increases and vagal influence decreases. Additionally, the low and high frequency bands have been assumed to be related to sympathetic and vagal influence, respectively. Based on these assumptions, the concept of a spectral ratio of these two bands, indicative of this implied balance, was adopted as a potentially useful metric for risk stratification. Because of the low predictive value of the ratio, teachings of Verrier et al. in U.S. Pat. No. 5,437,285 are predicated upon this ratio of low and high frequency components in combination with other metrics for assessing myocardial instability.
Although the concept of a balance between the two components of the autonomic system has been a widely embraced, and presumed to be quantified through a HRV spectral ratio, some studies show that calculations of such a balance of control may not be useful. One study by Eckberg (1997), for example, finds that vagal contributions to baseline low frequency RR-interval fluctuations are great, and evidence that baseline low frequency RR-interval spectral power is related quantitatively to sympathetic-cardiac nerve traffic is nonexistent. This same study concludes that calculations of sympathovagal balance may obscure rather than illuminate human physiology and pathophysiology.
As noted by Kannankeril et al. (2002), risk of SCD is about 17 times higher during or immediately following exercise than at rest. Kannankeril et al. also finds that the vagal influence of heart rate decreases with exercise, and that it appears likely that poor return of vagal control in the post exercise recovery period may be a very critical factor in the progression from instability to fatal arrhythmia.
Although the above described methods for measuring heart rate variability are well known to practitioners of the art and it also is recognized that the patient risk profile may be substantially unveiled during vigorous exercise and recovery, there is no effective method based on HRV for quantifying patient risk from heart rate data collected during exercise and recovery. Therefore, existing methods and apparatus for quantifying risk of SCD based on HRV do not provide an accurate low cost screening tool for mass screening.